Obesity Hinders TNFi treatment for Axial Spondyloarthritis

An association between obesity and psoriatic arthritis has been established. “Regarding obesity and axial spondyloarthritis (axSpA), there were only a few studies investigating this topic, and especially the response to tumor necrosis factor inhibitors (TNFi) in obese patients,” says Raphael Micheroli, of the rheumatology department at Zurich University Hospital.

He and fellow Swiss researchers, writing in Arthritis Research & Therapy, found an association between obesity and “significantly lower” response rates to TNF inhibitors in axSpA patients.

Axial spondyloarthritis causes spinal and pelvic inflammation as well as inflammatory back pain in 2.7 million Americans, according to the Spondylitis Association of America. TNF inhibitors target proteins that signal the body in ways that lead to inflammation.

Asked what surprised him the most during the research process, Dr. Micheroli says that he and colleagues found a trend where obese patients fared better in one benchmark — called Assessment in SpondyloArthritis international Society 40 percent (ASAS40) — when treated with infliximab than they did with other TNF inhibitors.

But that bucked the broader research trend. After one year of the first use of a TNF inhibitor, patients with normal body mass index (BMI) achieved a 40 improvement in disease at a rate of 44 percent, compared to 34 percent of overweight patients, and 29 percent of obese patients. (Normal BMI is defined as 18.5 to 25; overweight as 25 to 30; and obese as above 30; 332 patients in the study had normal BMI, while 204 were overweight, and 88 were obese.)

The study featured a large cohort from the Swiss Clinical Quality Management: 624 axSpA patients, and the 40 percent improvement corresponds to the Assessment in SpondyloArthritis international Society 40% (ASAS40).

“While being overweight decreased the odds of achieving an ASAS40 response upon TNF inhibition by about 30 percent, the odds were decreased by 70 percent in obese patients,” the authors write.
[Learn more about spondyloarthritis assessments]

The average age of the patients in the study was 39-years-old. “Compared with those of normal weight, those who were obese were older (age 43.2 versus 37.4),” reports <em>Medpage. The TNF inhibitors used in the study were as follows:

Adalimumab (humira) in 34.5 percent of cases

Etanercept (enbrel) in 26.7 percent of cases

Infliximab in 21.9% percent of cases

Golimumab (simponi) in 16.9 percent of cases

Certolizumab (cimzia) in less than 0.1 percent

After a year, the normal weight group saw a decline in something called the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of 5.3 to 2.9. The overweight patients saw a decline from 5.6 to 3.2, and the obese group dropped from 6.1 to 4.1.

“Potential reasons for the decreased efficacy associated with obesity include the possibility of underdosing in the TNF inhibitors that are not dosed according to weight, and the increased production of proinflammatory adipokines by fat tissue,” Medscape reported.

“The authors noted that patients with axial spondyloarthritis might benefit from weight loss both to improve their cardiovascular risk profile and to increase their therapeutic response, particularly in light of evidence that anti-TNF treatment has been associated with weight gain in spondyloarthritis,” it added.